Defining the role of RANK in skeletal diseases associated with osteoclast dysfunction

定义 RANK 在与破骨细胞功能障碍相关的骨骼疾病中的作用

• 批准号: G1000435/1
• 负责人: Julie Crockett
• 金额: $ 51.17万
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1000435%2F1
• 关键词: Defining; role; RANK; skeletal; diseases

Receptor Activator of NFkB (RANK) is an important molecule within cells that break down bone called osteoclasts. Throughout life, osteoclasts work together with cells that form bone to keep bones healthy and strong. Many diseases occur when osteoclasts do not work properly which leads to either too much or not enough bone being broken down. This makes the bones weak and easily fractured. We are studying rare diseases that affect babies, children and young adults and are caused by changes in the gene for RANK. These diseases are osteopetrosis (that is caused by a lack of osteoclast formation) and early-onset Pagetic diseases (that are caused by overactive osteoclasts). In the laboratory, we are hoping to learn about which parts of the RANK molecule are most important for osteoclasts to form and work properly. Osteoporosis is a common disease where too much bone is broken down leading to bones that are less dense, weak and fracture easily, which causes a lot of pain and discomfort. In addition, the healthcare costs associated with the treatment of osteoporosis are #6 million per day. It is therefore important that we identify people at risk before their bones become weak and start to fracture. We will look at the RANK gene in a group of people who have had the density of their bones measured and identify whether there are any changes in the gene that can be linked to people with low bone density. This information will then be used to assemble a list of changes within RANK that, if present, can help to predict which people are likely to develop osteoporosis.

NFkB受体激活剂(RANK)是细胞内一种重要的分子，它可以分解被称为破骨细胞的骨骼。在整个生命过程中，破骨细胞与形成骨骼的细胞一起工作，以保持骨骼的健康和强壮。当破骨细胞不能正常工作时，许多疾病就会发生，这会导致过多或不足的骨骼被分解。这会使骨骼变得脆弱，容易骨折。我们正在研究影响婴儿、儿童和年轻人的罕见疾病，这些疾病是由排名基因的变化引起的。这些疾病是骨腐症(由破骨细胞缺乏形成引起)和早发性传播性疾病(由过度活跃的破骨细胞引起)。在实验室中，我们希望了解RANK分子的哪些部分对破骨细胞的形成和正常工作最重要。骨质疏松症是一种常见的疾病，太多的骨骼被分解，导致骨骼不那么致密，脆弱，容易骨折，这会导致许多疼痛和不适。此外，与治疗骨质疏松症相关的医疗费用为每天600万英镑。因此，重要的是，我们必须在人们的骨骼变得脆弱并开始骨折之前识别出他们处于危险之中。我们将观察一组人的RANK基因，这些人已经测量了他们的骨骼密度，并确定该基因是否有任何变化与骨密度低的人有关。然后，这些信息将被用来收集排名内的变化列表，如果存在，可以帮助预测哪些人可能患上骨质疏松症。